91AV

Researchers at the 91AV who have been studying the side effects of drugs for more than a decade have discovered that antipsychotic drugs are getting into bone marrow, making it difficult for them to fight off infections.

Antipsychotic medications, such as Risperidone, are some of the most highly prescribed drugs in the United States. They are widely prescribed for diverse psychiatric conditions including schizophrenia, bipolar disorder and depression. They are also prescribed “off-label” for many conditions where they have not been proven to have a beneficial effect. Clinical reports indicate that schizophrenics have three times the risk of infection compared to population norms, but the role medications play in these risks has never been clear.

In a , the researchers showed that the psychiatric drug Risperidone infiltrates bone marrow in concentrations higher than found in the bloodstream. The bone marrow is where most of our immune system cells are born, develop and mature.

Karen Houseknecht, Ph.D., associate provost for Research and Scholarship and senior author on the study, discovered that psychiatric drugs can be found in bone marrow of experimental animals while examining the effects of psychiatric drugs on bone health. This led her to hypothesize that high drug concentrations in bone marrow may impact the biology of the cells found in marrow, including immune cell function, and can result in increased susceptibility to infection. Houseknecht, a pharmacologist who has been studying the metabolic side effects of antipsychotic drugs, including increased risk for diabetes and bone fractures, reached out to her colleague Meghan May, Ph.D., an infectious disease specialist, to help address this important question.

In their study, researchers treated healthy mice with these drugs for four weeks. Risperidone concentrations in the marrow of the mice were 10 to 15 times higher than in the bloodstream. After five days of treatment, Risperidone treatment blocked cell receptors instead of activating them, preventing defense against twenty-one different infectious diseases.

“I couldn't believe how impacted these animals were,” said May, a professor of microbiology and infectious disease in the 91AV College of Osteopathic Medicine, and one of the study’s authors. “The immune cells in the mice who were given the drug were either very immature looking and not effective or they were dead. The reason why it was so jaw dropping to me was that the dose we gave them was on the low end.”

The data are consistent with increased susceptibility to infection in patients administered these medications and can have profound implications for off-label prescribing to vulnerable patient populations including children and the elderly.  “Understanding the adverse side effects of these important psychiatric health medications is crucial in informing prescribing practices and patient monitoring to ensure better health outcomes,” said Houseknecht.

This first study has already led to further research involving a large group of students, including undergraduate, medical, and international exchange graduate students at 91AV.